Scientific Contributions

1997-Present

The quantitative nature of deficits in reciprocal social behavior

Our SDS laboratory developed and advanced methods for measuring variation in reciprocal social behavior as a quantitative trait, by devising a new system of questionnaire-based measurement, the Social Responsiveness Scale, now in its second edition.

The SRS-2 has been translated into over 30 foreign languages and is used worldwide as a standard for rapid, feasible quantitative ascertainment of autistic traits. This has allowed patterns of transmission of autistic social impairments to be traced in families and populations. These studies have helped elucidate the factoral and genetic structure of autistic syndromes, and the nature of the pronounced sex ratio observed for most forms of autism.

Most recently these measurements have proven capable of specifying elevations in offspring risk for autism and variation in social-adaptive functioning across diverse child psychiatric syndromes. These findings have significant implications for gene discovery, the identification of molecular targets for biological intervention, genetic counselling, and preventing functional impairment incurred by psychiatric conditions of childhood.

From a twin-study, this graph depicts the continuous distribution of autistic traits in the general population as measured using the Social Responsiveness Scale, which was designed in the Social Developmental Studies (SDS) Laboratory.

In the late 1990’s, the SDS laboratory led a series of studies in collaboration with the National Institutes of Health Clinical Laboratory, which demonstrated that variations in CSF 5-HIAA, the principal metabolite of serotonin, when ascertained in the neonatal period, was associated with inherited liability to antisocial behavior and to future development of aggression.

The magnitude of the association clarified that multiple factors were at play in mediating both inherited liability and early syndromes of antisocial behavior. These findings have stood the test of time and have, in turn, stimulated a prevention approach in which families of children who are particularly vulnerable to the deleterious effects of adverse life experience are targeted for the provision of strategic supports.

The Genetic Structure of Autism and Related Disorders

The rapid evolution of genomic technologies, coupled with the development of large registries and study samples related to autism created opportunities to integrate quantitative assessment methods with genetically-informative studies designed to elucidate the biological causes of autism.

Our SDS laboratory designed and executed a series of studies that were uniquely characterized by the inclusion of both affected and unaffected individuals in families of children with autism, who could be feasibly phenotyped for sub clinical autistic traits using the quantitative trait measures designed by our laboratory. This resulted in substantially increased statistical power to specify patterns of intergenerational transmission and molecular genetic variants that conferred risk to autism.

One of the remarkable findings that arose from this approach was the phenomenon of sex-based modulation of inherited liability to the social impairment of autism, the so-called “female protective effect,” which appears to underlie the universally-observed 4:1 male:female sex ratio in autism spectrum disorders. These findings have critically informed and enhanced gene discovery efforts, the identification of “carrier” states in unaffected females, and have motivated a next generation of experiments in our laboratory (and others), designed to understand the nature of sex-based modulation of inherited liability to autism.

Given that this phenomenon operates across a vast and heterogeneous array of newly-identified genetic pathways to autism, understanding of its biology carries with it the prospect of the identification of novel treatment approaches that might emulate this effect in a majority of males affected by familial ASD syndromes.

Results of a linkage analysis demonstrating association between genetic markers along chromosome 8 and reciprocal social behavior in children in families affected by autism.

Social Attachment, Psychopathology, and the Prevention of Child Maltreatment

In addition to our work on genetic susceptibility, a continuous theme of our SDS laboratory has been the characterization and prevention of environmental (i.e. non-inherited) influences on risk and resilience for social impairment in childhood. Our studies have helped to clarify the highly influential roles of a) insecure attachment; and b) child maltreatment on antisocial development in childhood, by uniquely controlling for the effects of inherited influence on behavioral outcome.

This research has established the rationale for pragmatic approaches to the simultaneous prevention of child abuse and promotion of social attachment among young children at risk for antisocial development. A first series of studies demonstrated the success of novel methods to engage families of high-risk infants in potent preventive intervention (eg. paraprofessional home visitation), and a meta-analysis demonstrated that parent-focused interventions that reduce antisocial behaviors in children are equally effective among those with and without inherited liabilities.

These efforts have laid the groundwork for a comprehensive approach to identifying and supporting the families of young infants at risk for antisocial development, which is currently being tested through active grants from the U.S. Administration for Children and Families and from municipal government sources. An ongoing effort to prevent child maltreatment recidivism for young children in foster care, the SYNCHRONY Project, is an active collaboration between our Division, the St. Louis County Family Court, and the Missouri Department of Social Services.